MOHITO, a novel mouse cytokine-dependent T-cell line, enables studies of oncogenic signaling in the T-cell context

Haematologica. 2011 May;96(5):779-83. doi: 10.3324/haematol.2010.035931. Epub 2010 Dec 29.

Abstract

The mouse pro-B cell line Ba/F3 has gained major interest as a model system to investigate oncogenic tyrosine kinases and to determine the efficacy of kinase inhibitors. While Ba/F3 cells are suitable to study oncogenic kinases derived from various cell types, the signaling networks in Ba/F3 cells are B-cell specific. We have established a mouse CD4+CD8+ double positive T-cell line (named MOHITO, for MOuse Hematopoietic Interleukin-dependent cell line of T-cell Origin) that has many features of human T-cell acute lymphoblastic leukemia (Notch1 and Jak1 mutation, TCR rearrangement) and is dependent on interleukin-7. The MOHITO cell line can be transformed to cytokine independent proliferation by BCR-ABL1 or mutant JAK1. This mouse T-cell line is a novel model system to investigate protein signaling and inhibition in a T-cell specific context and is a valuable tool to study and verify oncogenic capacity of mutations in the kinome and phosphatome in T-cell malignancies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Blotting, Western
  • CD4 Antigens / metabolism
  • CD8 Antigens / metabolism
  • Carcinogens / metabolism*
  • Cell Line
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Female
  • Fusion Proteins, bcr-abl / genetics
  • Fusion Proteins, bcr-abl / metabolism
  • HEK293 Cells
  • Humans
  • In Situ Hybridization, Fluorescence
  • Interleukin-7 / metabolism*
  • Interleukin-7 / pharmacology
  • Janus Kinase 1 / genetics
  • Janus Kinase 1 / metabolism
  • Karyotyping
  • Mice
  • Mice, Inbred BALB C
  • Mutation
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / genetics
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / metabolism
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / pathology
  • Receptor, Notch1 / genetics
  • Receptor, Notch1 / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction*
  • T-Lymphocytes / metabolism*

Substances

  • CD4 Antigens
  • CD8 Antigens
  • Carcinogens
  • Interleukin-7
  • Receptor, Notch1
  • Fusion Proteins, bcr-abl
  • Janus Kinase 1